Effect of Tiotropium Plus Salmeterol vs. Fluticasone/Salmeterol on Static Lung Volumes and Exercise Endurance in COPD

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00530842
First received: September 17, 2007
Last updated: November 27, 2013
Last verified: September 2013
  Purpose

The primary objective of this study is to demonstrate that treatment with a free combination of tiotropium and salmeterol provides superior improvement in static lung volumes and exercise tolerance compared to a fixed combination of fluticasone and salmeterol in patients with COPD.

The secondary objective includes assessment of safety.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Tiotropium plus Salmeterol
Drug: Fluticasone/Salmeterol
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
Official Title: Effect of Inhalation of a Free Combination of Tiotropium Once Daily 18 Mcg and Salmeterol Twice Daily 50 Mcg Versus a Fixed Combination of Fluticasone and Salmeterol Twice Daily (500/50 Mcg) on Static Lung Volumes and Exercise Tolerance in COPD Patients (a Randomised, Double-blind, Double Dummy, 16 (2 x 8) Weeks, Crossover Study).

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Post-dose TGV(FRC) (After 8 Weeks) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose TGV(FRC) (Thoracic Gas Volume; co-primary endpoint) after 8 weeks

  • Endurance Time (After 8 Weeks) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Endurance time to the point of symptom limitation after 8 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)


Secondary Outcome Measures:
  • Post-dose TGV(FRC) (After 4 Weeks) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose TGV(FRC) (Thoracic Gas Volume) after 4 weeks

  • Endurance Time (After 4 Weeks) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Endurance time to the point of symptom limitation after 4 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)

  • Static Lung Volumes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough TGV(FRC) (Thoracic Gas Volume) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough TGV(FRC) (Thoracic Gas Volume) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough RV (Residual Volume) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough RV (Residual Volume) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose RV (Residual Volume) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose RV (Residual Volume) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough IC (Inspiratory Capacity) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough IC (Inspiratory Capacity) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose IC (Inspiratory Capacity) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose IC (Inspiratory Capacity) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough IRV (Inspiratory Reserve Volume) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough IRV (Inspiratory Reserve Volume) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose IRV (Inspiratory Reserve Volume) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose IRV (Inspiratory Reserve Volume) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough TLC (Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough TLC (Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose TLC (Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose TLC (Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes (Percent) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough RV/TLC (Residual Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes (Percent) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough RV/TLC (Residual Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes (Percent) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose RV/TLC (Residual Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes (Percent) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose RV/TLC (Residual Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes (Percent) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes (Percent) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes (Percent) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)

  • Static Lung Volumes (Percent) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)

  • Slow Vital Capacity (SVC) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough SVC (Slow Vital Capacity) after 8 weeks (measured by spirometry)

  • Slow Vital Capacity (SVC) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough SVC (Slow Vital Capacity) after 4 weeks (measured by spirometry)

  • Slow Vital Capacity (SVC) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose SVC (Slow Vital Capacity) after 8 weeks (measured by spirometry)

  • Slow Vital Capacity (SVC) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose SVC (Slow Vital Capacity) after 4 weeks (measured by spirometry)

  • Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough FEV1 (Forced Expiratory Volume in 1 second) after 8 weeks (measured by spirometry)

  • Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough FEV1 (Forced Expiratory Volume in 1 second) after 4 weeks (measured by spirometry)

  • Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose FEV1 (Forced Expiratory Volume in 1 second) after 8 weeks (measured by spirometry)

  • Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose FEV1 (Forced Expiratory Volume in 1 second) after 4 weeks (measured by spirometry)

  • Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 8 weeks (measured by spirometry)

  • Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 4 weeks (measured by spirometry)

  • Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 8 weeks (measured by spirometry)

  • Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 4 weeks (measured by spirometry)

  • Forced Vital Capacity (FVC) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)

  • Forced Vital Capacity (FVC) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)

  • Forced Vital Capacity (FVC) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)

  • Forced Vital Capacity (FVC) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)

  • FEV1 Over FVC (Percent) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Trough FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)

  • FEV1 Over FVC (Percent) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Trough FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)

  • FEV1 Over FVC (Percent) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Post-dose FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)

  • FEV1 Over FVC (Percent) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Post-dose FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)

  • Symptom Intensity During Exercise [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Isotime Borg dyspnea scale after 8 weeks, Unit on a Scale (min. 0, max 10), 0 = no dyspnea, 10 = worst imaginable dyspnea

  • Symptom Intensity During Exercise [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Isotime Borg dyspnea scale after 4 weeks, Unit on a Scale (min. 0, max. 10), 0 = no dyspnea, 10 = worst imaginable dyspnea

  • Symptom Intensity During Exercise [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Isotime Borg leg discomfort scale after 8 weeks, Unit on a Scale (min. 0, max. 10), 0 = no leg dyscomfort, 10 = worst imaginable leg dyscomfort

  • Symptom Intensity During Exercise [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Isotime Borg leg discomfort scale after 4 weeks, Unit on a Scale (min. 0, max. 10), 0 = no leg dyscomfort, 10 = worst imaginable leg dyscomfort

  • Dyspnea and Leg Discomfort [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Peak Borg dyspnea scale after 8 weeks, Unit on a Scale (min. 0, max 10)

  • Dyspnea and Leg Discomfort [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Peak Borg leg discomfort scale after 8 weeks, Unit on a Scale (min. 0, max 10)

  • Locus of Symptom Limitation at Peak Exercise During Exercise [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Reason for stopping exercise at baseline (leg discomfort, breathing discomfort, both or none)

  • Locus of Symptom Limitation at Peak Exercise During Exercise [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Reason for stopping exercise after 4 weeks (leg discomfort, breathing discomfort, both or none)

  • Locus of Symptom Limitation at Peak Exercise During Exercise [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Reason for stopping exercise after 8 weeks (leg discomfort, breathing discomfort, both or none)


Enrollment: 344
Study Start Date: September 2007
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The patient has signed an Informed Consent Form in accordance with GCP and local legislative requirements prior to participation in the trial, i.e., prior to pre-trial washout of any restricted medications.
  2. The patient has a clinical diagnosis of chronic obstructive pulmonary disease (COPD).
  3. The patient has relatively stable, moderate to severe airway obstruction.
  4. The patient has a pre-bronchodilator forced expiratory volume in the first second (FEV1) less than or equal to 65% of predicted normal determined at Visit 1 using the following predicted equations (R94-1408):

    1. Males Forced expiratory volume in the first second (FEV1) predicted [Litres (L)] = 4.30 x Height [metres] minus 0.029 x Age [years] minus 2.49
    2. Females Forced expiratory volume in the first second (FEV1) predicted [Litres (L)] = 3.95 x Height [metres] minus 0.025 x Age [years] minus 2.60 and a Thoracic Gas Volume (Functional residual volume) ((TGV)(FRC)) bigger than 120% predicted normal at visit 1 (or historical data not older than 6 month)
    3. Males Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. [Litres (L)] = 2.34 x Height [metres] + 0.009 x Age [years] minus 1.09
    4. Females Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. [Litres (L)] = 2.24 x Height [metres] + 0.001 x Age [years] minus 1.00
  5. The patient is at least 40 years and less than or equal to 75 years old.
  6. The patient has a cigarette smoking history of at least 10 pack-years. A pack-year is defined as the equivalent of smoking one pack of cigarettes per day for a year.
  7. The patient is able to perform all specified procedures and able to maintain all necessary records during the study period as required in the protocol.
  8. The patient is able to inhale the trial medication from the HandiHaler device.
  9. The patient is able to inhale the trial medication from the Diskus/Accuhaler device.

Exclusion Criteria:

  1. a significant disease other than chronic obstructive pulmonary disease (COPD). (review contraindications for exercise testing),
  2. a recent history of myocardial infarction within one year.
  3. a recent history of heart failure, pulmonary oedema, or patients with cardiac arrhythmia or any contraindication to exercise described in the CTProtocol within the last 3.
  4. daytime supplemental oxygen.
  5. a diagnosis of known active tuberculosis.
  6. a history of cancer within the last 5 years.
  7. a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
  8. thoracotomy with pulmonary resection.
  9. an upper respiratory tract infection or an exacerbation of chronic obstructive pulmonary disease (COPD)
  10. a known hypersensitivity to anticholinergic drug, ß-adrenergic or corticosteroids, lactose or any other component of the inhalation capsule delivery system.
  11. a known symptomatic prostatic hypertrophy or bladder neck obstruction.
  12. a known moderate or severe renal insufficiency.
  13. a known narrow-angle glaucoma.
  14. a known untreated hypokalemia.
  15. a known untreated thyrotoxicosis.
  16. a history of asthma, allergic rhinitis or atopy, or a total blood eosinophil count larger than 600/mm3.
  17. treatment with cromolyn sodium or nedocromil sodium
  18. treatment with antihistamines or antileukotrienes.
  19. treatment with tiotropium for 1 month before Visit 1.
  20. treatment with oral corticosteroid medication.
  21. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception
  22. a history of or active alcohol or drug abuse.
  23. an investigational drug within 1 month or 10 half lives
  24. a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea.
  25. participation in a rehabilitation program for chronic obstructive pulmonary disease (COPD).
  26. treatment with monoamine oxidase inhibitors inhibitors or tricyclic antidepressants.
  27. participation in another study.
  28. more than eight puffs of salbutamol/day during the run-in period
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00530842

  Show 42 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00530842     History of Changes
Other Study ID Numbers: 205.334
Study First Received: September 17, 2007
Results First Received: December 30, 2009
Last Updated: November 27, 2013
Health Authority: Austria: Bundesamt für Sicherheit im Gesundheitswesen, A-1030 Vienna
Canada: Health Canada, Therapeutic Products Directorate
France: Agence Française de Sécurité Sanitaire des Produits de Santé 143-147 boulevard Anatole France 93285
Germany: BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte)
Italy: Comitato Etico per la Sperimentazione Clinica dei Medicinali dell'A.O. Univ. Pisana di Pisa
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
Sweden: Medical Products Agency Regional Ethics Committee of Uppsala
United States: Food and Drug Administration

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Lung Diseases, Obstructive
Pathologic Processes
Respiratory Tract Diseases
Albuterol
Fluticasone
Fluticasone, salmeterol drug combination
Salmeterol
Tiotropium
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Allergic Agents
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Cholinergic Agents
Cholinergic Antagonists
Dermatologic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Parasympatholytics

ClinicalTrials.gov processed this record on October 21, 2014